As the clinical importance of non-alcoholic fatty liver disease (NAFLD) is increasingly appreciated, research is focusing on distinguishing its subtypes and staging the extent of hepatic fibrosis. At one end of the NAFLD spectrum is simple steatosis (SS), and at the other end are non-alcoholic steatohepatitis (NASH), and NASH-related cirrhosis and fibrosis. The distinction between NASH and simple steatosis is important because of differences in their potential for progression. Generally, simple steatosis is relatively benign, but NASH can progress to cirrhosis and fibrosis.
NAFLD is generally asymptomatic until severe liver impairment occurs. The costs associated with managing patients with NASH can be substantial, emphasizing the importance of early diagnosis of NASH. If recognized, treatment methods for NAFLD and NASH can slow or reverse the disease in some individuals, particularly in early stage disease.
There are no laboratory tests for NAFLD or NASH. Serum aminotransferase elevations and hepatic imaging studies showing changes suggestive of fatty liver are not adequate alone or in combination to distinguish NAFLD from NASH. At present, liver biopsy with strict pathologic criteria is the only method to accurately establish the diagnosis of NASH or to stage the extent of fibrosis. Despite important technological improvements (for example, automatic biopsy guns, ultrasound guidance), liver biopsy remains costly and is associated with potentially important complications that occur in approximately 0.5% of cases. Additionally, histologic lesions of NASH may not be evenly distributed throughout the liver parenchyma, leading to sampling errors. An inadequate length or fragmented biopsy specimen can make the correct diagnosis even more challenging.
Alternatives to liver biopsy include non-invasive radiological modalities such as ultrasound, computerized tomography, and magnetic resonance imaging. Unfortunately, most of these modalities can only detect hepatic steatosis and are unable to distinguish NASH from simple steatosis or accurately detect hepatic fibrosis. There remains a need for non-invasive methods of detecting and screening for NAFLD and NASH. What is needed are better methods for diagnosing NAFLD and NASH, monitoring disease progression, and determining efficacy of treatment. Additionally, what is needed are better testing methods that can be used to classify and differentiate between subjects with NAFLD and NASH, and to identify subjects at risk of transitioning from NAFLD to NASH.